This study was designed to test analgesia, duration, and cardiovascular changes induced by meperidine (MEP) and oxymorphone (OXY) following methoxyflurane (MOF) and halothane (HAL) anesthesia. Eight healthy dogs were given atropine and acepromazine, and anesthesia was induced with thiamylal and maintained with 1.5 minimal alveolar concentration of MOF or HAL for 1 hour during controlled ventilation. Eight treatments were given with each anesthetic: 3 with MEP (0.5, 1.0, and 2.0 mg/kg, IV), 3 with oxymorphone (OXY; 0.05, 0.1, and 0.2 mg/kg, IV), and 2 placebos with sterile water. Test drugs were given at the end of anesthesia when early signs of recovery were evident. Minimal threshold stimulus/response nociception was assessed by use of an inflatable soft plastic colonic balloon. Blood pressures and pulse rate were measured with a noninvasive monitor. Meperidine and OXY were found to be effective analgesics and could be reversed with naloxone. Intravenous administration of 2.0 mg of MEP/kg provided analgesia for 36 +/- 6 minutes and 39 +/- 15 minutes after MOF and HAL, respectively. In contrast, OXY was effective at all 3 doses with effects of IV administration of 0.2 mg of OXY/kg lasting 154 +/- 13 minutes and 152 +/- 12 minutes, after MOF and HAL, respectively. Analgesia could not be demonstrated after anesthesia for acepromazine, MOF, or HAL. Blood pressure was not changed by either anesthetic nor was it influenced by MEP or OXY. Pulse rate was significantly depressed by the higher doses of OXY following HAL, but was not changed by MEP following either anesthetic. This study demonstrated the longer duration of analgesia of OXY. In addition, we could not find that analgesia was provided by either MOF or HAL following recovery from anesthesia.

Effects of ketamine, xylazine, and a combination of ketamine and xylazine were studied in 12 male Pekin ducks (7 to 12 weeks old; mean [+/- SD] body weight, 3.1 +/- 0.3 kg). After venous and arterial catheterization and fixation of a temperature probe in the cloaca, each awake duck was confined, but not restrained, in an open box in a dimly lit room. Blood pressure and lead-II ECG were recorded. Three arterial blood samples were collected every 15 minutes over a 45-minute period (control period) and were analyzed for pHa, Paco2 and Pao2. After the control period, each duck was assigned at random to 1 of 3 drug groups: (1) ketamine (KET; 20 mg/kg of body weight, IV), (2) xylazine (XYL; 1 mg/kg, IV), and (3) KET + XYL (KET 20 mg/kg and XYL, 1 mg/kg; IV). Measurements were made at 1, 5, 10, 15, 30, 45, 60, and 90 minutes after drug administration. All ducks survived the drug study. Cloacal temperature was significantly (P less than or equal to 0.05) increased above control cloacal temperature at 90 minutes after the administration of ketamine, and from 10 through 90 minutes after administration of ketamine plus xylazine. In ducks of the KET group, pHa, Paco2, and Pao2, remained unchanged after administration of the drug. In ducks of the XYL group, pHa and Pao2 decreased significantly (P less than or equal to 0.05) from control values for all time points up to and including 15 minutes after drug administration. In ducks of the KET + XYL group, pHa and Pa02 were significantly (P less than or equal to 0.05) decreased at all time points up to and including 45 and 15 minutes, respectively, after administration of the drugs. In ducks of the XYL group, Paco2 increased significantly (P less than 0.05) during the first 15 min. after drug administration, and for 45 min. after administration of KET + XYL. Results indicated that ketamine when given alone to ducks, was not associated with pulmonary depression.

Dispositions of caffeine and antipyrine were compared as indicators of decreasing hepatic function in dogs with experimentally induced progressive liver disease. Dimethylnitrosamine, a hepatospecific toxin, was administered orally to 16 dogs; 6 dogs served as controls (group 1). Three classes of liver disease were defined by histologic features: mild (group 2; n = 5), moderate (group 3; n = 6), and severe (group 4; n = 5). Disposition of antipyrine, and 24 hours later, caffeine was studied 3 weeks after the last dose of toxin in each dog. For both drugs, rapid IV administration of 20 mg/kg of body weight was administered and serum samples were obtained at intervals for determination of at least 5 terminal-phase drug half-lives. For both drugs, clearance and mean residence time differed among groups (P less than or equal to 0.01). Clearance of antipyrine and caffeine was decreased in groups 3 and 4, compared with groups 1 and 2. Antipyrine and caffeine mean residence times were longer in group-3 dogs, compared with dogs of groups 1 and 2. Correction of caffeine and antipyrine clearances for hepatic weight increased discrimination between groups 3 and 4. The clearance and mean residence time ratios of antipyrine to caffeine were calculated for each group and, when compared with values for group-1 dogs, were used to test for differences between the 2 drugs in response to disease. Ratios did not differ among groups. These results indicate that the disposition of antipyrine and caffeine may change similarly with progression of dimethylnitrosamine-induced liver disease.

We compared the ability of 2 alpha2-adrenergic receptor antagonists, atipamezole and yohimbine, to reverse medetomidine-induced CNS depression and cardiorespiratory changes in lambs. Twenty lambs (7.8 +/- 2.6 kg) were randomly allotted to 4 treatment groups (n = 5). Each lamb was given medetomidine (30 micrograms/kg of body weight, IV), followed in 15 minutes by IV administration of atipamezole (30 or 60 micrograms/kg), yohimbine (1 mg/kg), or 0.9% NaCl (saline) solution. Medetomidine caused lateral recumbency in 1 to 2 minutes in all treated lambs. Medetomidine significantly (P < 0.05) decreased heart rate at 5 and 10 minutes after its administration. Heart rate remained above 120 beats/min, and severe bradycardia (< 70 beats/min) and other arrhythmias did not occur throughout the study. Medetomidine also induced tachypnea in all treated lambs. The tachypnea was abolished by atipamezole and yohimbine, but not by saline solution administration. The medetomidine-induced tachypnea did not significantly affect arterial pH and PaCO2. Arterial oxygen tension was within acceptable range (PaO2 = 71 to 62 mm of Hg), but was lower than expected. Administration of atipamezole, yohimbine, or saline solution did not change PaO2 significantly. Lambs treated with 30 or 60 micrograms of atipamezole/kg were able to walk unassisted in 2.4 +/- 0.4 and 2.3 +/- 0.7 minutes, respectively, whereas yohimbine-and saline-treated lambs did not walk unassisted until 15.6 +/- 2.7 and 73.0 +/- 6.8 minutes later, respectively. Results of this study indicated that medetomidine is a potent CNS depressant in lambs. Atipamezole at dosage of 30 or 60 micrograms/kg was equally effective, and was more effective in antagonizing medetomidine-induced CNS depression than was yohimbine.

Eight adult female cattle (6 Holstein, 1 Jersey, 1 Brown Swiss) were used to determine the antagonistic effects of tolazoline, an alpha 2-adrenoceptor antagonist, on xylazine-induced (via caudal epidural administration) depression of CNS, respiratory, and cardiovascular activity and rumen motility. A 2% solution of xylazine HCl was injected into the epidural space at the first coccygeal interspace, using a dosage of 0.05 mg/kg of body weight, diluted to a 5-ml volume with sterile water, and administered at a rate of approximately 1 ml/30 s. Eight minutes after xylazine injection, either tolazoline (0.3 mg/kg) or saline solution (4 ml) was administered IV. All 8 cattle were treated, using both regimens in a random sequence; at least 1 week elapsed between treatments. Epidurally administered xylazine induced caudal analgesia (S3 to coccyx), as evaluated by no response to superficial and deep muscular pinprick, and induced sedation, cardiopulmonary depression, and inhibition of rumen motility, but all cattle remained standing. Tolazoline effectively reversed xylazine-induced rumen hypomotility, and partially antagonized xylazine-induced cardiopulmonary depression without affecting sedation and desirable local (S3 to coccyx) analgesic effects.

Pharmacologic effects of alpha-methylfentanyl and 3-methylfentanyl, analogs of fentanyl, were investigated in mares. The ability of an 125I-labeled fentanyl radioimmunoassay (125I-RIA) to detect these methylated fentanyl analogs in individual and pooled urine samples from horses was evaluated. Also, the ability of 7 fentanyl antibodies to react with fentanyl and fentanyl derivatives (sufentanil, alfentanil, and carfentanil) was investigated. Mares were studied in a locomotor test to determine the amount of stimulation methylated fentanyl analogs might induce. Two mares each were given alpha-methylfentanyl at 1, 2, 4, 8, or 13 microgram/kg of body weight, IV, or 3-methylfentanyl at 0.4, 0.7, or 1 microgram/kg IV. The cross-reactivity of sufentanil, alfentanil, carfentanil, alpha-methylfentanyl, and 3-methylfentanyl with 7 fentanyl antibodies was studied, using the 125I-RIA. All fentanyl analogs, with the exception of alfentanil, cross-reacted well with a C1 antibody raised to fentanyl. Less satisfactory cross-reactivity was determined with 6 other antibodies raised to fentanyl derivatives. When the C1 antibody was combined with an iodinated analog to fentanyl, good detectability of alpha-methylfentanyl and 3-methylfentanyl, in terms of fentanyl equivalents, was obtained from urine samples of dosed mares. The ability of the 125I-RIA to detect methylated fentanyl analogs in forensic urine samples pooled in groups of up to 20 samples was evaluated. When these methylated analogs were administered to mares in doses that induced measurable locomotor stimulation, the analog's presence was readily detected in individual or pooled samples.